Local Control of Blood Flow

1. Local Control of Blood Flow

2. Reading Klabunde, Cardiovascular Physiology Concepts Chapter 7 (Organ Blood Flow) pages 141-151.

3. Regulation of Peripheral Blood Flow Dual Control Extrinsic Primarily by the nervous system Humorally also Intrinsic (Locally in the tissues) Controlled by the conditions in the immediate vicinity of the blood vessels

4. Regulation of Peripheral Blood Flow

5. Pharmacologic Stimuli that Cause Contraction or Relaxation of Vascular Smooth Muscle Catecholamines Epinephrine Norepinephrine Dopamine Endothelin Serotonin Angiotensin II Vasopressin Histamine Adenosine Nitric Oxide (NO) Carbon Dioxide Potassium Hydrogen Ion Prostaglandins Acetylcholine Bradykinin

6. Intrinsic Control of Local Blood Flow:Metabolic Factors

7. Tissue Metabolic Activity Is the Main Factor in Acute Control of Local Blood Flow One of the most fundamental principles of circulatory function is the ability of each tissue to control its own local blood flow in proportion to its metabolic needs Metabolic Mechanism Any intervention that results in an inadequate oxygen (nutrient) supply for the metabolic requirements of the tissues results in the formation of vasodilator substances which increase blood flow to the tissues.

8. Acute Local Feedback Control of Blood Flow

9. Metabolic Mechanisms Hypoxia Tissue metabolites and ions Adenosine Potassium ions Carbon dioxide Hydrogen ion Lactic acid Inorganic phosphate

10. Examples of Metabolic Control of Local Bloodflow Active Hyperemia Reactive Hyperemia

11. Active Hyperemia

12. Reactive Hyperemia

13. Reactive Hyperemia Within limits the peak blood flow and the duration of the of the reactive hyperemia are proportional to the duration of the occlusion

14. Intrinsic Control of Local Blood Flow:Autoregulation

15. Autoregulation Intrinsic ability of an organ to maintain a constant blood flow despite changes in perfusion pressure Possible explanations for Autoregulation: Myogenic Mechanism Metabolic Mechanism

16. Ohm�s Law

17. Cerebral Autoregulation

18. Autoregulation

19. Theories to Explain Autoregulation:Myogenic Mechanism When the lumen of a blood vessel is suddenly expanded, the smooth muscles respond by contracting in order to restore the vessel diameter and resistance. The converse is also true. Vascular smooth muscle cells depolarize when stretched. Proposed mechanism is stretch of vascular smooth muscle causes activation of membrane calcium channels.

20. Theories to Explain Autoregulation:Myogenic Mechanism

21. Theories to Explain Autoregulation:Metabolic Mechanism When the pressure increases to a tissue, the flow increases, and excess oxygen and nutrients are provided to the tissues. These excess nutrients cause the blood vessels to constrict and the flow to return nearly to normal despite the increased pressure.

22. Intrinsic Control of Local Blood Flow:Endothelial Factors

23. The endothelium plays an active role in regulating the microcirculation Endothelium is a source of substances that elicit contraction or relaxation of the vascular smooth muscle Vasoactive substances released from endothelium: Nitric Oxide (NO) Endothelium-derived relaxing factor Prostacyclin Endothelin Endothelial-derived hyperpolarizing factor (EDHF)

25. Nitric Oxide

26. Nitric Oxide Generated from amino acid L-arginine Generated from NO synthase Increases GMP concentration which produces relaxation by decreasing cytosolic free calcium Very short half-life (6 seconds) Due to rapid oxidation to nitrite and nitrate Also due to binding by substances such as hemoglobin NO is a gas and must be delivered by an inhaled delivery system

27. Nitric Oxide NO production is stimulated by: Shearing forces acting on the endothelium Acetylcholine Bradykinin Histamine Insulin Substance P

28. Nitric Oxide Important functions in cardiovascular system: Vasodilation Inhibition of vasoconstrictor influences Inhibition of platelet adhesion to the vascular endothelium Inhibition of leukocyte adhesion to the vascular endothelium Antiproliferative Free radical scavenger

29. Nitric Oxide Systemic Effects: Pulmonary vasodilation Decreased pulmonary vascular resistance Decreased pulmonary artery pressure Pulmonary vasodilation decreases right ventricular afterload and improves right ventricular performance Increased arterial oxygen tension Inhaled nitric oxide is delivered only to ventilated alveoli. This improves V/Q relations by vasodilating capillaries and improving blood flow to areas participating in gas exchange.

30. Nitric Oxide

31. Prostacyclin

32. Prostacyclin Prostacyclin synthase in endothelial cells acts on cyclo-endoperoxide products to form Prostacyclin (PGI2) Prostacyclin (PGI2) Strong vasodilator Inhibits platelet adhesion to the vascular endothelium

33. Endothelin

34. Endothelin Synthesized by endothelium Potent vasoconstrictor Other actions: Increased aldosterone secretion Increased cardiac inotropy and chronotropy Decreased renal blood flow and GFR Releases atrial natriuretic peptide In failing heart, contributes to calcium overload and hypertrophy

35. Endothelin Implicated in the pathogenesis of: Hypertension Vasospasm Heart failure Pulmonary hypertension

36. When Damage to Endothelium Occurs Damage to endothelial cells will lead to: Decreased Nitric Oxide and Prostacyclin production Increased Endothelin production This will lead to: Vasoconstriction Vasospasm Thrombosis

37. THE END